We propose a multi-faceted program to investigate the molecular basis o the transformation of cells by DNA viruses. Specific programs include genetic and molecular approaches to the analysis of host proteins interacting with BPV E5 and ras oncogenes, and host proteins determining the differential susceptibility of transformed cells to parvovirus infection. Other projects concern the analysis of transforming genes of EBV and of novel methods by which herpesviruses may modulate host cell gene expression, studies of the interaction between oncogenes and host DNA sequences, and an approach to defining cell pathways and the action of oncogenes in transforming keratinocytes and melanocytes and the possible modulation of the transformed properties of individual cells by surrounding normal cells. A core provides administrative support and support for common equipment and facilities. This program represents a Yale Medical School that has been in operation for fourteen years.